Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors

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ClinicalTrials.gov Identifier: NCT00112619

Recruitment Status
:
Terminated
(Slow accrual and company withdrawing support to supply the drug)

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.

Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the target pharmacokinetic parameter.

PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24 months.

Estimate the maximum tolerated dose of intraventricular topotecan on this schedule [ Time Frame: First 14 days of therapy ]

Number of patients with dose-limiting toxicity [ Time Frame: First 14 days of therapy ]

Estimate the dose of intraventricular topotecan that will result in cerebrospinal fluid lactone concentrations exceeding 1 ng/mL for at least 8 hours after an intrathecal injection [ Time Frame: Day 1 of Week 1 ]

Secondary Outcome Measures
:

Number of patients with objective documentation of tumor response to intraventricular topotecan [ Time Frame: Weeks 5, 11 and then every 12 weeks until off study ]

MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.

Pharmacokinetics [ Time Frame: Day 1 of Week 1 ]

The cerebrospinal fluid (CSF) concentration-time profile for topotecan after intrathecal CSF administration will be modeled from the CSF samples collected on day 1 of week 1. Individual pharmacokinetic parameters estimated will include volume of central compartment, elimination rate constant, half-life, and clearance.

Correlation of imaging parameters with tumor response [ Time Frame: Pre-treatment, week 5, week 11, and then every 12 weeks until off study ]

MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.

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